ABSTRACT:4-amino-1-[(2R,3R,4S,5S)-3,4,5-trihydroxytetrahydrofuran-2-yl]-1,3,5-triazin-2(1H)-one (azacitidine) is an anti-cancer chemotherapy drug mainly used in the treatment of myelodysplastic syndrome (MDS). Azacitidine is a chemical analogue of the cytosine, a nucleoside found in DNA and RNA. Conformational analysis and geometry optimization of azacitidine was performed according to the Hartree-Fock (HF) calculation method by ArgusLab 4.0.1 software. Molecular mechanics calculations were based on specific interactions within the molecule. These interactions included stretching or compressing of bond beyond their equilibrium lengths and angles, torsional effects of twisting about single bonds, the Vander Waals attractions or repulsions of atoms that came close together, and the electrostatic interactions between partial charges azacitidine due to polar bonds. Surface created to visualize ground state properties as well as excited state properties such as orbital, electron densities, electrostatic potential (ESP) spin densities. The generated grid data were used to make molecular orbital surface, visualized the molecular orbital, electrostatic potential map and electron density surface. The steric energy for azacitidine was calculated to be 0.12162642 a.u.( 76.32179805 kcal/mol). It was concluded that the lowest energy and most stable conformation of azacitidine was 0.12162642 a.u.( 76.32179805 kcal/mol) The most energetically favourable conformation of azacitidine was found to have a heat of formation of 157.6452 kcal/mol. The self-consistent field (SCF) energy was calculated by geometry convergence function using RHF/PM3 method in ArgusLab software. The most feasible position for azacitidine to induce antineoplastic activity in the receptor was found to be -110.6126839099 au (- 69410.5697 kcal/mol)